ANH and NPA ask the FDA to reverse its position and not exclude NMN from dietary supplement definition.

Nicotinamide mononucleotide (NMN) has gained popularity as a dietary supplement due to its often-reported ability to boost cellular energy production and protect against aging-related diseases. However, the regulatory status of NMN supplements has been a source of controversy, with the US Food and Drug Administration (FDA) declaring that NMN can no longer be sold as a dietary supplement in the US.

Longevity.Technology: The FDA’s decision was catalyzed by clinical-stage pharma company Metro International Biotech‘s researching NMN as a drug. The company is working on “small-molecule NAD+ enhancers that leverage the NAD+ cycle to treat rare diseases and pursue significant improvements in human health to combat the adverse conditions of aging”, and a molecule that is a drug cannot be a supplement.

One of the consequences of the FDA’s declaration was retail behemoth Amazon’s decision to no longer sell NMN unless labelled with National Drug Code information – a decision that sent shockwaves through the longevity supplements industry. This is hardly surprising given that the global NMN market, which was valued at US$253 million in 2020, is projected to reach US$386 million by the end of 2027 [1].

However, the supplements industry isn’t taking the FDA’s decision lying down.

Two industry groups, the Alliance for Natural Health (ANH) and the Natural Products Association (NPA), have submitted a citizen petition to the FDA requesting that the agency reverse its position on NMN supplements [2]. Specifically, they have called on the agency to recognize NMN as a dietary ingredient and to allow its use in supplements without requiring pre-market approval.

NMN and NAD+

NMN is a precursor to nicotinamide adenine dinucleotide (NAD+), a molecule that plays a crucial role in cellular metabolism. NAD+ is involved in several key processes, including glycolysis (the breakdown of glucose for energy), the citric acid cycle (which generates ATP, the primary energy currency of cells), and oxidative phosphorylation (which produces additional ATP). As we age, our bodies produce less NAD+, which can lead to a decline in cellular energy production and an increased risk of age-related diseases. Supplementing with NMN is thought to increase NAD+ levels and, in turn, improve cellular energy production and promote healthy aging.

Indeed, several studies have investigated the potential benefits of NMN supplementation in animals and humans. In a study published in the journal Cell Metabolism, researchers gave NMN to a group of old mice and found that it reversed several age-related physiological declines, including mitochondrial dysfunction, inflammation and insulin resistance [3]. Similar findings have been reported in other animal studies, including a study in which NMN improved muscle function in aged mice.

Human studies have been more limited, but the results so far are promising; in a small study published in the journal Nature Communications, researchers gave NMN to a group of healthy adults and found that it increased NAD+ levels and improved markers of cardiovascular health [4]. Another study found that NMN supplementation improved insulin sensitivity in people with prediabetes.

What the FDA is saying about NMN

So far, so longevity, but despite the growing body of scientific evidence supporting the potential benefits of NMN supplementation, the regulatory status of NMN supplements has proven to be a point of contention. In the US, dietary supplements are regulated by the FDA under the Dietary Supplement Health and Education Act (DSHEA) of 1994. Under this law, dietary supplements are generally not subject to pre-market approval by the FDA, as long as they contain ingredients that are “generally recognized as safe” (GRAS) and meet certain other requirements.

However, now the FDA has taken the position that NMN does not meet the definition of a dietary ingredient under DSHEA and should be classified as a drug. This classification would require NMN supplements to undergo more rigorous testing and approval processes – similar to those required for prescription drugs. This is despite NMN being available as supplement for many years.

Arguments for and against

In their citizen petition, the ANH and NPA argue that NMN should be recognized as a dietary ingredient and allowed in supplements without pre-market approval. They point to the fact that NMN occurs naturally in foods such as broccoli, avocado, and cabbage, and that it has a long history of use as a dietary supplement in Japan. Citing several studies showing that NMN is safe and well-tolerated in humans, the petitioners make the point that NMN has numerous potential health benefits.

The ANH and NPA’s petition has received support from some industry groups and supplement manufacturers, who argue that the FDA’s position on NMN supplements is overly restrictive and could stifle innovation and consumer access to potentially beneficial supplements.

As with so many things, however, there is a flipside.

Some experts have expressed concern about the safety and efficacy of NMN supplements, arguing that the studies conducted so far have been small and of short duration, and that more research is needed to determine the long-term effects of NMN supplementation. With so many supplement sellers crowding the marketplace, questions about quality and purity of NMN supplements on the market have been raised, as well as the appropriate dosages and potential interactions with other medications.

As yet, the FDA has not yet responded to the ANH and NPA’s citizen petition, and it remains to be seen whether the agency will change its position on NMN supplements.

The controversy over NMN supplements highlights the challenges of regulating dietary supplements in a rapidly-evolving landscape of scientific and consumer trends. As new research emerges on the potential benefits and risks of supplements like NMN, regulators will need to strike a balance between ensuring safety and efficacy, while also preserving consumer choice and access to innovative products that could improve lifespan and healthspan.

[1] https://www.precisionreports.co/global-nicotinamide-mononucleotide-nmn-sales-market-17556260
[2] https://www.nutraingredients-usa.com/content/download/834445/16231300
[3] https://www.cell.com/cell-metabolism/fulltext/S1550-4131(11)00346-9
[4] https://www.nature.com/articles/s41598-023-29787-3